Laboratory of Pharmaceutical Technology, Department of Pharmacy, CIRM, University of Liège, Av. de l'Hôpital 1, Liège, Belgium.
J Pharm Biomed Anal. 2011 Mar 25;54(4):694-700. doi: 10.1016/j.jpba.2010.10.022. Epub 2010 Nov 3.
The European Pharmacopoeia describes a liquid chromatography (LC) method for the quantification of sulindac, using a quaternary mobile phase including chloroform and with a rather long run time. In the present study, a new method using a short sub-2 μm column, which can be used on a classical HPLC system, was developed. The new LC conditions (without chloroform) were optimised by means of a new methodology based on design of experiments in order to obtain an optimal separation. Four factors were studied: the duration of the initial isocratic step, the percentage of organic modifier at the beginning of the gradient, the percentage of organic modifier at the end of the gradient and the gradient time. The optimal condition allows the separation of sulindac and of its 3 related impurities in 6 min instead of 18 min. Finally, the method was successfully validated using an accuracy profile approach in order to demonstrate its ability to accurately quantify these compounds.
《欧洲药典》描述了一种使用包含氯仿的四元流动相并具有较长运行时间的液相色谱（LC）方法来定量舒林酸。在本研究中，开发了一种新方法，使用可以在经典 HPLC 系统上使用的短亚 2μm 柱。通过基于实验设计的新方法对新的 LC 条件（不含氯仿）进行了优化，以获得最佳分离。研究了四个因素：初始等度步骤的持续时间、梯度开始时有机改性剂的百分比、梯度结束时有机改性剂的百分比和梯度时间。最佳条件允许舒林酸及其 3 种相关杂质在 6 分钟内分离，而不是 18 分钟。最后，使用准确度概况方法成功验证了该方法，以证明其能够准确定量这些化合物的能力。
